Background <p>The major target for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is widely expressed in the cardiovascular system, leading to vascular endothelial cell damage and inflammation. The aim of present study is to investigate impacts of Omicron on arterial structure and stiffness using longitudinal data with matched controls.</p> Methods <p>In this longitudinal study, we collected clinical characteristics and laboratory values from participants recovered after COVID-19 infections during the Omicron wave (<i>n</i> = 45) and matched uninfected controls (<i>n</i> = 85) around the time of 2022 change in control measures. Corresponding baseline data in 2021 were included for repeated analyses. Carotid arterial properties, including intima-media thickness (IMT), diameter, stiffness and wave reflections were integratively assessed by ultrasound based on the raw radio frequency signal.</p> Results <p>Clinical characteristics and carotid properties were matched between COVID-19 and control groups at baseline. Carotid IMT was thicker in recovered participants than controls (567 ± 97 vs. 532 ± 88&#xa0;μm, <i>P</i> = 0.037) at the follow-up of 2022, while no significant differences were found for the diameter, arterial stiffness and wave reflections in the two groups. Repeated ANOVA further revealed that COVID-19 infection was associated with higher increase of carotid IMT and concomitant concentric remodeling in comparison with controls (<i>P</i>_{time × COVID−19} &lt; 0.01).</p> Conclusions <p>Carotid structure is changed in recovered study participants of COVID-19 during the Omicron wave, featured by increased IMT and concentric remodeling. On the other hand, arterial stiffness and wave reflections seemed unimpacted by the Omicron variant. Whether the Omicron related carotid structure change is permanent or temporary needs further investigation by long-term follow-up.</p> Graphical Abstract <p></p>